FuZhengHuaYuJiangZhuTongLuoFang Prescription Modulates Gut Microbiota and Gut-Derived Metabolites in UUO Rats

Abstract

BackgroundAlteration of intestinal flora and metabolites is closely related to chronic kidney disease (CKD) across early to advanced stages. FuZhengHuaYuJiangZhuTongLuoFang prescription (FZHY) is a Chinese herb that has been proven to effectively treat CKD, but the underlying mechanism is not clear.MethodsRats were subjected to intragastric treatment with FZHY 7, 14, and 21 days after unilateral ureteral obstruction (UUO) surgery, and kidney tissue, colon tissue, serum, and stool samples were collected.ResultsFZHY treatment effectively ameliorated UUO-induced renal function loss, renal injury and renal fibrosis, and colon tissue damage and fibrosis on day 7. The results of 16S flora analysis (day 7) showed that, compared with the UUO group, both the FZHY group and the sham group showed decreased levels of g_Monoglobus, g_Papillibacter, g_Eubacterium_nodatum, and g_Family_XIII_AD3011. Additionally, FZHY obviously induced the reduction of serum citrulline, glycoursodeoxycholic acid, 23-nordeoxycholic acid, 7-ketodeoxycholic acid, kahweol, lipoid B4, 4-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-2-methyl-1,3-thiazole, taurolithocholic acid sodium salt, indoline-2-carboxylic acid, 5(S),15(S)-diHETE, and others and the increase of bilirubin, asparagine, and others, which were positively associated with the above four candidate bacteria. Moreover, FZHY increased the levels of ZO-1, occludin, and claudin-1 in the colonic mucosa and reduced the levels of CRP, TNF-α, IL-6, and IL-1 in the serum and LN, FN, Col-I, and Col-III in the tubulointerstitium of UUO rats on day 7.ConclusionOur study revealed that FZHY reduced kidney damage at the early stage of CKD by regulating the above four candidate bacteria biomarkers and gut-derived harmful metabolites, inhibiting the inflammation response and tubulointerstitial fibrosis, providing deep insight into CKD therapeutic strategy.

Kangxianling formula attenuates renal fibrosis by regulating gut microbiota

“…α-SMA, TGF-β, FN and Col-III are vital renal fibrosis-related proteins [ 18 ]. The activation of α-SMA, TGF-β, FN and Col-III caused by various factors contributed to exacerbation of organ fibrosis [ 19 ]. Col-III, a major component of ECM, and high expression of Col-III foster the generation of collagen fibers leading to ECM deposition in the kidney tissue and expediting renal fibrosis progression [ 20 ].…”

Colonic microflora and plasma metabolite-based comparative analysis of unilateral ureteral obstruction-induced chronic kidney disease after treatment with the Chinese medicine FuZhengHuaYuJiangZhuTongLuo and AST-120

“…AST-120 acts as a charcoal adsorbent that can directly clear uremic toxins in the kidney, such as IS, and causes secondary renoprotective effects, including rebalancing the flora and metabolism. In contrast, FZHY contains many active monomers, which not only absorb harmful metabolites from the intestine and inhibit the production of harmful metabolites but also alleviate tubulointerstitial fibrosis [ 67 ].…”

Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction

“…This may be associated with the compensatory function of the contralateral kidney at the early stage of UUO. The various UUO animal models reported in the literature are listed in Table 1 [8,9,11,12,[15][16][17][18][19][20][21][22].…”